Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system. It is a common cause of persistent disability in young adults. In patients suffering from MS, the immune system destroys the myelin sheet of axons in the brain and the spinal chord, causing a variety of neurological pathologies. In the most common form of MS, Relapsing-Remitting (RRMS), episodes of acute worsening of neurological function (exacerbations, attacks) are followed by partial or complete recovery periods (remissions) that are free of disease progression (stable).
In order to diagnose a patient with MS two separate events must be recorded. It has been reported that the majority of patients with MS initially present with a clinically isolated syndrome because of an inflammatory demyelinating lesion in the optic nerve, brain stem, or spinal cord. About 50 percent of those patients with a clinically isolated syndrome progress to clinically definite MS (CDMS) within 37 months of presentation. About 40-50% to progress to clinically definite MS within 18 months when assessment is made using magnetic resonance imaging (MRI). The subsequent progression of the disease can vary significantly from patient to patient. The progression can range from a benign course to a classic relapsing-remitting, chronic progressive, or rare fulminant course.
A method for diagnosing MS that facilitates early MS diagnosis and prediction of disease progression or level of activity (Benign, Moderate and Malignant) would be valuable for both managing the disease and providing counsel to the patient. For example, patients diagnosed early with an active MS course could be offered treatments that are beneficial for early MS. In addition, patients at risk for progressing faster and suffering from an additional clinical event in near future would benefit from a more aggressive treatment that will help to postpone these potential next events.
Current methods for assessment and tracking progress of MS are based on assessment and scoring of patients' function in attacks and accumulated disabilities during the attacks. One assessment used to assess MS is the Expanded Disability Status Scale (EDSS). However, the EDSS scoring system does not predict the progression of the disease. In addition, EDSS scoring can be variable because it is based on a subjective assessment of patient function. Methods for diagnosis can also include tracking brain lesions by MRI or testing Cerebrospinal Fluid (CSF) for Oligo-Clonal Banding (OCB). MRI is a physical method for assessment of brain lesions and is used widely for MS diagnosis. However, it typically offers only a very long term predictive value, and the correlation between MRI results and disease activity can be poor. Thus, MRI, OCB or any other existing test cannot be used for short term projections of disease progression, level of activity, or disease management.
Cerebrospinal puncture is an unpleasant invasive procedure that is not suitable for routine use or prognosis. In addition, both methods assess damage only after it has occurred; neither method can predict the onset of attacks or silent, sub-clinical lesions. A further disadvantage in the above-mentioned methods as a way to diagnose MS is that a negative OCB or MRI will not preclude the existence of MS.
Most patients with MS initially present with a clinically isolated syndrome (CIS). Despite the fact that MS will develop in up to 80% of these patients, the course of the disease and the time to conversion is unpredictable at its onset. The disease may remain inactive for many years before the appearance of a second clinical relapse or new lesions on an MRI confirm the diagnosis. Because currently available therapy is only partially effective and side effects are common, many neurologists are uncertain whether to treat all such patients with immunomodulators, or to wait until the diagnosis is confirmed by a second clinical event or the appearance of new MRI lesions. In addition, approved aggressive and potent therapy may not be used because of side effects associated with the therapy, the lack of information on the course of the disease and/or the expected disease progression.
There is a need for a simple serological assay that predicts: i) whether patients at First Neurological Event (FNE) or CIS suggestive of MS will develop MS in a certain timeframe: ii) whether a newly diagnosed relapsing remitting MS that will have a more active disease course and therefore may require aggressive treatment: or iii) whether newly diagnosed MS patient will follow a relatively benign course that allows the patient to postpone immunomodulatory therapy until necessary. This assay would be also useful in helping for diagnosing, assessing the progression of, and managing the treatment of MS. There is in addition an unmet need for developing specific serum based biomarkers for the diagnosis and prognosis of Relapsing Remitting MS (RRMS).